Long-term pharmacological and toxicological consequences of administration of narcotic agonists and antagonists used in narcotic treatment programs will be studied. The agonist 1-alpha-acetylmethadol (LAAM) and the antagonist naltrexone will be administered to mice, rats and guinea pigs. The effects of acute and chronic administration on the following parameters will be assessed: a) Hepatic, microsomal mixed function oxidases (such as cytochrome P-450 and aminopyrine N-demethylase) responsible for the metabolism of drugs; b) Testosterone delta 4-reductase, the rate limiting enzyme in testosterone metabolism, and plasma levels of testosterone; c) Myocardial function and sympathetic nervous system transmission; d) Dopamine receptor activity in the corpus striatum; and e) Various aspects of maternal behavior and opioid receptor activity. Naltrexone will be administered via subcutaneous implantation of naltrexone (2 mg)-containing beads consisting of a polylactic/polyglycolic acid copolymer (dynatech R/D Comp.). LAAM will be administered p.o. at doses found to be effective in the blockade of withdrawal signs in narcotic tolerant/dependent animals.